Process for separating beta-pyridyl nitrile and nicotinamide from an aqueous mixturecontaining nicotinic acid



Patented Aug. 3, 1954 PROCESS FOR SEPARATING fi-PYRIDYLNI- TRILE .AND. NICOTINAMIDE .FROM CAN AQUEOUS MIXTURE CONTAININGYNICO- TINIC ACID Roland G. Bonner, Bronxville, and Irving Hochhauser, Bronx, N. Y., assignors to Nepera' Chemical 00., Inc., Yonkers, N. Y., a corporation of New York No Drawing. Application March 13, 1952, Serial No. 276,444

9 Claims. 1

This invention relates to the separation of certain pyridine compounds and relates more par ticularly to the separation of nicotinic acid from a mixture containing nicotinic acid, B-pyridyl nitrile and nicotinamide.

An object of this invention is the provision of an efficient and economical process for the treatment of a crude mixture of nicotinamide and fi-pyridyl nitrile which also contains nicotinic acid whereby the nicotinamide and {i-pyridyl nitrile may be separated from the nicotinic acid.

Other objects of this invention will appear from the following detailed description.

In the production of nicotinamide by a process which involves the amidation of nicotinic acid with ammonia, the crude product of the amida- I a more complete separation is achieved if said tion reaction is obtained in a formwhich is tillate obtained during the catalytic dehydration step contains, in addition to the desired 3-pyridyl nitrile, some nicotinic acid, some unreacted nicotinamide and .also, an appreciable amount of the water of reaction. "An eiiective separation of the nicotinic acid from this aqueous mixture is important since it-remains unchanged when the purified nitrile undergoes hydrolysis to the amide and constitutes an undesirable impurity in the final product; However, purification of this mixture has proven to be a troublesome operation and a considerable amount of eiiort has been expendedin reaching a satisfactory-solu-- tion.

We have now found that the nicotinic acid present in a crude aqueous-mixture comprising nicotinic acid, B-pyridyl'nitrile and nicotinamide may be satisfactorily separated therefrom if the Yv crude aqueous mixture, while in an alkaline condition, is extracted with a water-immisciblehydrocarbon aromaticorganic solventsuch as, for example, benzene, the xylenes or toluene, employing the solvent in such amount that the conoentration of the p-pyridyl nitrile in the solvent is at least 30% by weight.v The nicotinic. acid,

remains behind in the raifinate or aqueous phase While both the nicotinamide and ,B-pyridyl nitrile are removed in the solvent phase. Although extraction is carried out in a plurality of stages, e. g. two or more, with the raffinate of each stage being subjected to further extraction during subsequent extractionstages. The extraction process may be conductedat all temperatures between the freezing point and boiling point of the constituents, but the preferred range is 25 to 50 C. Ordinarily, sufiicient ammonia distills over with the crude product during the catalytic dehydration of the nicotinamide and no further addition of. any alkaline agent is necessary to-maintain the crude aqueous distillate in an alkaline condition for. said extraction treatment. However, where, the distillate is not alkaline-it may be made: alkaline by the addition thereto of ammonia or caustic soda or any other soluble alkali;

In order further to illustrate the novel process of our invention, but without being limited thereto, the following exampleis given:

Example 100 parts by weight of a crude alkaline aqueous dehydration product, having a pH of above 7.0 obtained as the distillate of the catalytic dehydration of nicotinamide and consisting of 2G parts'by weight of water-and 80 parts by weight of a mixture of nicotinic acid, nicotinamide and ,B-pyridyl nitrile, the ratio of the latter mixture being about 5% by weight of nicotinic acid, 15% by weight of nicotinamide and 80% by weight of B-pyridyl nitrile, are mixed with 40* parts by weight of industrial grade xylene and strongly agitated for 10 minutes'ata temperature of about 35 C; The mixture is permitted to separate to form a xylene solution containing 50% by weight-of B-pyridyl nitrile' in which is dissolved 10% '-by weight of nicotinamide. Theiraffinate is allowed to separate and the extraction repeated twice'more with lO-parts byweight of xylene being employed for each of-said extraction steps. The xylene phases are combined andare found to contain over 98% of the B-pyridyl nitrile and r of the nicotinamide originally present in the crude mixture. The aqueous phase contains all of the nicotinic acid present in the crude mixture as well as some nicotinamide. The aqueous phase is preferably recycled to the amidation step of the process where the nicotinic acid present is converted to crude nicotinamide which is then converted to B-pyridyl nitrile. The xylene phase is treated with water and caustic soda in order to convert the nitrile to purified nicotinamide. Thus, the nicotinamide formed from the nitrile and the nicotinamide which is extracted by the xylene are obtained in the form of a solution from which both can be crystallized out as U. S. P. nicotinamide. Our novel process enables nicotinamide to be obtained in a very high degree of purity and completely ac ceptable for all commercial uses.

It is to be understood that the foregoing detailed description is given merely by way of illustration and that many variations may be made therein without departing from the spirit of our invention.

Having described our invention, what we desire to secure by Letters Patent is:

We claim:

3.. In a process for separating fi-pyridyl nitrile and nicotinamide from an aqueous mixture of said compounds containing nicotinic acid as an impurity, the step which comprises extracting the B-pyridyl nitrile and nicotinamide from said aqueous mixture while the latter is in an alkaline condition employing a water-immiscible aromatic organic solvent selected from the group consisting of benzene, toluene, and the xylenes in such amount as to form an organic solvent solution of c-pyridyl nitrile in which nicotinamide is soluble and containing at least 30% by weight of c-pyr idyl nitrile.

2. In a process for separating B-pyridyl nitrile and nicotinamide from an aqueous mixture of said compounds containing nicotinic acid as an impurity, the step which comprises extracting the c-pyridyl nitrile and nicotinamide from said aqueous mixture while the latter is in an alkaline condition employing a water-immiscible aromatic organic solvent selected from the group consisting of benzene, toluene, and the xylenes in such amount as to form an organic solvent solution of [3-pyridyl nitrile in which nicotinamide is soluble and containing from 50 to 60% by weight of c-pyridyl nitrile.

3. In a process for separating ,B-pyridyl nitrile and nicotinamide from an aqueous mixture of said compounds containing nicotinic acid as an impurity, the step which comprises extracting the [3-pyridyl nitrile and nicotinamide from said aqueous mixture while the latter is in an alkaline condition employing benzene as the extractant, the benzene being employed in such amount as to form a benzene solution of ii-pyridyl nitrile in which nicotinamide is soluble and containing from 50 to 60% by weight of B-pyridyl nitrile.

4. In a process for separating B-pyridyl nitrile and nicotinamide from an aqueous mixture of said compounds containing nicotinic acid as an impurity, the step which comprises extracting the c-pyridyl nitrile and nicotinamide from said aqueous mixture while the latter is in an alkaline condition employing toluene as the extractant, 70

the toluene being employed in such amount as to form a toluene solution of fi-pyridyl nitrile in which nicotinamide is soluble and containing from to by weight of fi-pyridyl nitrile.

5. In a process for separating B-pyridyl nitrile and nicotinamide from an aqueous mixture of said compounds containing nicotinic acid as an impurity, the step which comprises extracting the B-pyridyl nitrile and nicotinamide from said aqueous mixture while the latter is in an alkaline condition employing Xylene as the extractant, the xylene being employed in such amount as to form a xylene solution of c-pyridyl nitrile in which nicotinamide is soluble and containing from 50 to 60% by Weight of c-pyridyl nitrile.

6. In a process for separating B-pyridyl nitrile and nicotinamide from an aqueous mixture of said compounds containing nicotinic acid as an impurity, the step which comprises subjecting said aqueous mixture to a plurality of extractions to remove the fi-pyridyl nitrile and nicotinamide therefrom while said aqueous mixture is in an alkaline condition employing a water-immiscible aromatic organic solvent selected from the group consisting of benzene, toluene, and the xylenes, the amount of said solvent which is employed in each stage being such as to form an organic solvent solution of ,B-pyridyl nitrile in which nicotinamide is soluble and containing at least 30% by weight of [i-pyridyl nitrile.

7. In a process for separating e-pyridyl nitrile and nicotinamide from an aqueous mixture of said compounds containing nicotinic acid as an impurity, the step which comprises subjecting said aqueous mixture to a plurality of extractions to remove the B-pyridyl nitrile and nicotinamide therefrom while said aqueous mixture is in an alkaline condition employing benzene as the extractant, the benzene being employed in such amount in each stage as to form a benzene solution of c-pyridyl nitrile in which nicotinamide is soluble and containing from 50 to 60% by weight of B-pyridyl nitrile.

8. In a process for separating B-pyridyl nitrile and nicotinamide from an aqueous mixture of said compounds containing nicotinic acid as an impurity, the step which comprises subjecting said aqueous mixture to a plurality of extractions to remove the B-pyridyl nitrile and nicotinamide therefrom while said aqueous mixture is in an alkaline condition employing toluene as the extractant, the toluene being employed in such amount in each stage as to form a toluene solution of B-pyridyl nitrile in which nicotinamide is soluble and containing from 50 to 60% by weight of s-pyridyl nitrile.

9. In a process for separating ,B-pyri-dyl nitrile and nicotinamide from an aqueous mixture of said compounds containing nicotinic: acid as an impurity, the step which comprises subjecting said aqueous mixture to a plurality of extractions to remove the fi-pyridyl nitrile and nicotinamide therefrom while said aqueous mixture is in an alkaline condition employing xylene as the extractant, the xylene being employed in such amount in each stage as to form a xylene solution of p-pyridyl nitrile in which nicotinamide is soluble and containing from 50 to 60% by weight of B-pyridyl nitrile.

References Cited in the file of this patent UNITED STATES PATENTS Number Name Date 2,436,660 Mueller Feb. 24', 1948 2,471,518 Duesel et al. May 31, 1949 2,491,253 Crossley et al, Dec. 13, 19% 2,496,114 Berg Jan. 31, 1950 

6. IN A PROCESS FOR SEPARATING B-PYRIDYL NITRILE AND NICOTINAMIDE FROM AN AQUEOUS MIXTURE OF SAID COMPOUNDS CONTAINING NICOTINIC ACID AS AN IMPURITY, THE STEP WHICH COMPRISES SUBJECTING SAID AQUEOUS MIXTURE TO A PLURALITY OF EXTRACTIONS TO REMOVE THE B-PYRIDYL NITRILE AND NICOTUNAMIDE THEREFROM WHILE SAID AQUEOUS MIXTURE IS IN AN ALKALINE CONDITION EMPLOYING A WATER-IMMISCIBLE AROMATIC ORGANIC SOLVENT SELECTED FROM THE GROUP CONSISTING OF BENZENE, TOLUENE, AND THE XYLENES, THE AMOUNT OF SAID SOLVENT WHICH IS EMPLOYED IN EACH STAGE BEING SUCH AS TO FORM AN ORGANIC SOLVENT SOLUTION OF B-PYRIDYL NITRILE IN WHICH NICOTINAMIDE IS SOLUBLE AND CONTAINING AT LEAST 30% BY WEIGHT OF B-PYRIDYL NITRILE. 